
www.sciam.com SCIENTIFIC AMERICAN 41
Remarkably, it appears that the adult mouth can provide a
suitable environment for tooth development. That is just one
of the three milestones toward engineering replacement teeth
that we identifi ed earlier, however. The road to human bioen-
gineered teeth may yet have a few twists.
On the Cusp
compared with efforts to engineer other organs,
teeth have made considerable progress in a short time. The
overall challenge remains developing methods that are simple
yet controlled.
Another of the targets that we established, the ability to
predict and control tooth size and shape, is close. In cultured
primordia, molar and incisor tooth germs can easily be dis-
tinguished by their appearance and their gene activity, al-
though other shapes found in the human mouth, such as pre-
molars and canines, are more diffi cult.
The teeth grown from embryonic primordia in the mouths
of adult mice by the Sharpe group displayed shapes appropri-
ate to their original locations in the embryo—molar primor-
dia grew into molar-shaped teeth, for example. Because shape
signals are received at the very start of natural tooth develop-
ment, the embryonic tooth germs were already programmed.
Tissue engineers need to better understand these initial shape
signals to induce them in human bioteeth.
To date, the teeth generated by any of the tissue engineer-
ing methods we have described have not developed roots. In
truth, both root development and the stimuli that initiate tooth
eruption are complex and still little understood. Roots are the
last part of teeth to form, completing their development during
the eruption process, and more research is needed to under-
stand what conditions would best favor their creation in re-
placement teeth. Another unknown is how long engineered
human teeth would take to fully form in an adult mouth. Hu-
mans’ second set of “adult” teeth also begins developing in the
embryo, yet those teeth take six to seven years to fi nally
erupt—or 20 years in the case of wisdom teeth. Our experience
with tooth generation in animals suggests that an engineered
human tooth would form far more quickly, but we do not
know if it might take longer to fully mature and its enamel to
completely harden.
Of course, most research into bioengineered tooth pro-
duction is also working toward fi nding an effective and easily
accessible source of the patient’s own cells to use as raw mate-
rial. Immune rejection would be avoided, and because tooth
size, shape and color are genetically determined, the engi-
neered teeth would more closely match the patient’s natural
teeth. The Sharpe group has found that adult mesenchymal
stem cells derived from bone marrow (but also possibly ob-
tainable from fat) can replace embryonic mesenchyme in the
tooth formation process. A substitute for embryonic epithe-
lium has yet to be identifi ed, although purported adult stem
cells have been discovered in other tissues with epithelial ori-
gins, such as skin and hair. These or some other adult cell type
may prove effective, perhaps with the aid of gene manipulation
to induce the appropriate initiating signals for odontogenesis.
Of the several potential cell sources, teeth themselves may
be the most convenient. The Forsyth group’s results suggest
that stem cells capable of forming tooth tissues, including
enamel, could be present within teeth. Researchers elsewhere
have also shown that dentin and other tooth tissues experience
some natural regeneration after injury, which, too, suggests
the presence of progenitor cells capable of generating a variety
of tooth tissues. Thus, the possibility exists of someday soon
fashioning new teeth from old.
MORE TO EXPLORE
Tissue Engineering: The Challenges Ahead. Robert S. Langer and
Joseph P. Vacanti in Scientifi c American, Vol. 280, No. 4, pages 86–89;
April 1999.
Tissue Engineering of Complex Tooth Structures on Biodegradable
Polymer Scaffolds. Conan S. Young, Shinichi Terada, Joseph P. Vacanti,
Masaki Honda, John D. Bartlett and Pamela C. Yelick in Journal of Dental
Research, Vol. 81, No. 10, pages 695–700; October 2002.
Bioengineered Teeth from Cultured Rat Tooth Bud Cells. Monica T.
Duailibi, Silvio E. Duailibi, Conan S. Young, John D. Bartlett, Joseph P.
Vacanti and Pamela C. Yelick in Journal of Dental Research, Vol. 83,
No. 7, pages 523–528; July 2004.
Stem Cell Based Tissue Engineering of Murine Teeth. A. Ohazama,
S.A.C. Modino, I. Miletich and P. T. Sharpe in Journal of Dental Research,
Vol. 83, No. 7, pages 518–522; July 2004.
The Cutting Edge of Mammalian Development: How the Embryo
Makes Teeth. Abigail S. Tucker and Paul T. Sharpe in Nature Reviews
Genetics, Vol. 5, No. 7, pages 499–508; July 2004.
MOUSE TOOTH grown from transplanted molar primordia
in the upper jaw of a host mouse demonstrates that new
teeth can develop in the adult mouth. The tooth at center in this cross
section of the jaw’s diastema region has broken through the gum line
(a second tooth above it and to the right is still forming). Pulp is visible
inside the emerged tooth. Red stain colors dental hard tissues,
highlighting enamel and dentin. Although lacking roots, the tooth is
attached to surrounding jawbone by soft connective tissue.
Connective
tissue
Jawbone
Dentin Pulp
Enamel
Gum
Tooth
MATT BRADMAN
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